Abstract
OBJECTIVE: Spinal cord (SC) atrophy correlates with and predicts the underlying progressive biology in active and non-active multiple sclerosis (MS), thereby providing a biomarker for clinical trials and patient management. Initiation of disease-modifying therapy (DMT) may be followed by early pronounced central nervous system (CNS) volume loss due to resolution of inflammation (pseudoatrophy) and confounding the interpretation of atrophy. High-dose glucocorticoids (HDGs) reduce inflammation and might therefore modify pseudoatrophy. METHODS: One hundred twenty-three newly diagnosed and DMT-naïve MS participants (relapsing-remitting, 70% female participants, median age = 36 years, Expanded Disability Status Scale [EDSS] 2.0) were followed for up to 3 years. Forty-two participants received HDG before baseline magnetic resonance imaging (MRI; DMT-HDG; median = 52 days, interquartile range [IQR] = 37-71), whereas 60 did not (DMT/no-HDG). Twenty-one participants remained untreated (no-DMT), and 102 started DMT after baseline MRI. SC total cervical cord cross-sectional area (TCA), gray matter area (GMA), and white matter area (WMA) and regional brain volumes were analyzed using mixed effects models. RESULTS: The DMT-HDG, DMT/no-HDG, and no-DMT groups had similar demographic, clinical, and radiological features. Pronounced SC pseudoatrophy was observed based on more year 1 versus year 2 volume loss for DMT/no-HDG (-2.06% vs. 0.83%; P = 0.02) but not DMT-HDG (-0.51% vs. 0.66%; P = 0.8) and more year 1 volume loss for DMT/no-HDG compared to DMT-HDG (-2.06% vs. 0.51%; P = 0.02). INTERPRETATION: HDG preceding baseline MRI suppresses CNS white matter (WM) pseudoatrophy after DMT initiation, most conspicuously for the SC. Suppression of pseudoatrophy with HDG may improve the fidelity of clinical trials and enhance the feasibility for short-term trials with SC and brain MRI outcomes in active MS by pretreatment with HDG. ANN NEUROL 2025;98:837-850.